Data from A Genome-Wide Scan Identifies Variants in <i>NFIB</i> Associated with Metastasis in Patients with Osteosarcoma

Abstract

<div>Abstract<p>Metastasis is the leading cause of death in patients with osteosarcoma, the most common pediatric bone malignancy. We conducted a multistage genome-wide association study of osteosarcoma metastasis at diagnosis in 935 osteosarcoma patients to determine whether germline genetic variation contributes to risk of metastasis. We identified an SNP, rs7034162, in <i>NFIB</i> significantly associated with metastasis in European osteosarcoma cases, as well as in cases of African and Brazilian ancestry (meta-analysis of all cases: <i>P</i> = 1.2 × 10<sup>−9</sup>; OR, 2.43; 95% confidence interval, 1.83–3.24). The risk allele was significantly associated with lowered <i>NFIB</i> expression, which led to increased osteosarcoma cell migration, proliferation, and colony formation. In addition, a transposon screen in mice identified a significant proportion of osteosarcomas harboring inactivating insertions in <i>Nfib</i> and with lowered NFIB expression. These data suggest that germline genetic variation at rs7034162 is important in osteosarcoma metastasis and that <i>NFIB</i> is an osteosarcoma metastasis susceptibility gene.</p><p><b>Significance:</b> Metastasis at diagnosis in osteosarcoma is the leading cause of death in these patients. Here we show data that are supportive for the <i>NFIB</i> locus as associated with metastatic potential in osteosarcoma. <i>Cancer Discov; 5(9); 920–31. ©2015 AACR</i>.</p><p>This article is highlighted in the In This Issue feature, p. 893</p></div>